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Indomethacin increases severity of Clostridium difficile infection in mouse model

Juan Muñoz-Miralles1,2, Bruno C Trindade3, Pablo Castro-Córdova1,2

  • 1Millennium Nucleus in the Biology of Intestinal Microbiota, Facultad de Ciencias de la Vida, Universidad Andrés Bello, 8370186 Santiago, Chile.

Future Microbiology
|September 22, 2018
PubMed
Abstract

Insights

The nonsteroidal anti-inflammatory drug indomethacin worsened Clostridium difficile infection (CDI) severity in mice, causing increased mortality and inflammation. Targeting prostaglandins may help reduce CDI severity.

Area of Science:

  • Microbiology and Immunology
  • Pharmacology

Background:

  • Clostridium difficile infection (CDI) is a significant healthcare-associated infection.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used medications with potential effects on inflammatory processes.

Purpose of the Study:

  • To investigate the impact of indomethacin, an NSAID, on the severity of antibiotic-associated Clostridium difficile infection (CDI) in a mouse model.

Main Methods:

  • Two mouse models of antibiotic-associated CDI were utilized across two facilities.
  • Mice were administered varying doses (low and high) of indomethacin.
  • Outcomes assessed included weight loss, clinical signs of infection, histopathological damage, mortality, and intestinal inflammatory markers (KC, IL-1β, IL-22).

Main Results:

  • Indomethacin administration led to significant weight loss, exacerbated signs of severe infection, and increased histopathological damage in CDI models.
  • A 100% mortality rate was observed in indomethacin-treated mice during CDI.
  • Indomethacin-treated mice exhibited enhanced intestinal inflammation, with elevated expression of KC, IL-1β, and IL-22 compared to controls.

Conclusions:

  • NSAID administration, specifically indomethacin, negatively impacts antibiotic-associated CDI severity in mice.
  • Targeting prostaglandin synthesis or signaling pathways presents a potential therapeutic strategy for ameliorating CDI severity.
Keywords:
C. difficile infection severityNSAIDantibiotic-associated CDIindomethacinprostaglandins

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